The brown recluse spider is commonly found throughout the midsouth region of the United States. Bites from the brown recluse occur when the spider is trapped in clothing or its nest is otherwise disturbed. The bite may be undetected by the patient until hours or days later when a characteristic lesion develops. Mild reactions to envenomation are usually limited to a lesion only. In some cases, a severe reaction results which can be life-threatening. Although there have been case reports of various pharmacological agents used for the treatment of brown recluse bites, none have been shown to be consistently effective. Therapy for brown recluse bites remains centered around aggressive wound care. Early surgical excision has not been shown to be of benefit and in most cases delays healing. This review focuses on the physiological mechanisms of the brown recluse venom and current treatment options.